Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-nine IDDM patients with borderline hypertension were randomly allocated to placebo or nitrendipine treatment. Nitrendipine was given orally at a dosage of 20 mg once daily over 4 weeks. Stimulated platelet thromboxane formation at rest and after standardized, non exhausting exercise was measured by standard methods. In addition, plasma levels of platelet factor 4 and aggregation responses to collagen and ADP were determined. In the treatment group thromboxane formation after stimulation with collagen (0.3 and 1.0 micrograms/ml) and 1 mM arachidonic acid (AA) was reduced in the resting state. Exercise induced change of thromboxane synthesis in response to 1.0 micrograms/ml collagen was significantly lower as compared to placebo (p < 0.05). In parallel, PF4 plasma levels were significantly lowered (p < 0.05). Whole blood aggregation after collagen stimulation (1.0 micrograms/ml) was reduced after 4 weeks of nitrendipine treatment, but ADP (5 microM) induced aggregation was not. These effects of nitrendipine were not seen in platelet rich plasma. In conclusion long-term nitrendipine treatment may inhibit collagen dependent platelet activation in the blood of diabetic patients with borderline hypertension.
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PMID:Reduced platelet thromboxane formation after long-term administration of a dihydropyridine calcium channel blocker: a prospective, double-blind, placebo-controlled study with nitrendipine in borderline hypertensive patients with IDDM-type diabetes mellitus. 128 47

Pentosidine is an advanced glycosylation end product and protein cross-link that results from the reaction of pentoses with proteins. Recent data indicate that long-term glycation of proteins with glucose also leads to pentosidine formation through sugar fragmentation. In this study, the relationship between the severity of diabetic complications and pentosidine formation was investigated in collagen from skin-punch biopsies from 25 nondiabetic control subjects and 41 IDDM patients with diabetes duration greater than 17 yr. Pentosidine was significantly elevated in all IDDM patients versus control subjects (P less than 0.0001). It correlated strongly with age (P less than 0.0001) and weakly with duration (P less than 0.082). Age-adjusted pentosidine levels were highest in grade 2 (severe) versus grade 1 and 0 complication in all four parameters tested (retinopathy, proteinuria, arterial stiffness, and joint stiffness). Significant differences were found for retinopathy (P less than 0.014) and joint stiffness (P less than 0.041). The highest degree of association was with the cumulative grade of individual complication (P less than 0.005), determined by summing indexes of all four parameters. Pentosidine also was significantly elevated in the serum of IDDM patients compared with control subjects (P less than 0.0001), but levels were not significantly correlated with age, diabetes duration, complication, or skin collagen pentosidine (P greater than 0.05). A high correlation between pentosidine levels and long-wave collagen-linked fluorescence also was observed, suggesting that pentosidine is a generalized marker of accelerated tissue modification by the advanced glycosylation/Maillard reaction, which is enhanced in IDDM patients with severe complications.
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PMID:Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM. 139 2

Eight hundred patients with alopecia areata (AA) responded to a detailed questionnaire that was compiled, distributed, and analyzed by Help Alopecia International Research, Inc. (HAIR). Among those responding, 28% were men and 72% were women. Fifty percent had localized alopecia, 30% had alopecia totalis, and 20% had alopecia universalis. Forty-eight percent developed their initial onset before the age of 20. A very strong family history of 42% was found. There were 333 additional family members with AA. Many patients and relatives had concurrent atopic diseases (seasonal rhinitis, bronchial asthma, and atopic dermatitis). Associated autoimmune diseases including vitiligo, thyroid disease, and collagen vascular disease in patients and relatives appeared consistent with previous reports. Insulin dependent diabetes mellitus (IDDM) was not increased in patients but greatly increased in relatives. Additional analysis suggests a genetic association between the two diseases where expression of AA may prevent the development of IDDM.
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PMID:Profile of alopecia areata: a questionnaire analysis of patient and family. 156 16

1. In no ethnic group is the overall association between systemic sclerosis and the MHC strong enough for direct clinical use. MHC associations do support the classification of the disease into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. 2. Indications are that associations between specific subsets of patients with systemic sclerosis and genetic markers will assume greater importance both diagnostically and prognostically. The group with lung fibrosis look prime candidates, for example. 3. Genetic markers are useful means of relating chemically induced systemic sclerosis like disorders with the classical disease. Vinyl chloride disease provides an example. 4. Evidence is emerging of strong associations between certain genetic markers and autoantibody production; a similar story has emerged in systemic lupus erythematosus. We believe that, eventually, genetic tests will be used to influence treatment in at least a subset of patients with systemic sclerosis but that a dramatic breakthrough will not be made until we know how the genetics of the disease relate to the primary biochemical disease characteristic--that is, the overproduction of collagen. In this respect it has been suggested that the 5' flanking DNA of dermal collagen genes is particularly susceptible to the action of Scl-70 (topoisomerase I). A problem is how to tie this and the other observations discussed above together. The association of autoantibodies with topoisomerase I provides a tentative link between the MHC and collagen gene expression. Although the role and reason for anti-Scl-70 in systemic sclerosis is unknown, humoral autoimmunity, at least in systemic lupus erythematosus, seems to be strongly dependent on specific HLA genes. With an understanding of the function of MHC products at the molecular level, HLA and disease associations can now be analysed on a mechanistic level. For insulin dependent diabetes mellitus it has been shown that the MHC determined susceptibility to the disease is conferred by neutral residues (Val, Ser, Ala), at position 57 of the DQ beta chain, while Asp at this position correlates with resistance. A similar phenomenon has been described in rheumatoid arthritis. Although DR4 in general is associated with rheumatoid arthritis, it is heterogeneous, but a subtype of DR4 which is characterised by positively charged residues at positions 70 and 71 of the beta chains is not found in patients with rheumatoid arthritis (Wordsworth B P et al, unpublished data). A similar approach applied to the study of systemic sclerosis is likely to be similarly rewarding. The precise subtyping of the class II genes and the characterisation of their associated haplotypes is therefore required for a complete understanding of the contribution of the MHC to the disease. Additional genes linked to the MHC must not be overlooked, and are relevant to associations of haplotypes with the disease. Of particular interest are the recent reports of a new class of proteins, which are determined by genes in the MHC and which are considered to play a part in the assembly of the antigen peptide/MHC molecule complex.
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PMID:Major histocompatibility complex class II genes and systemic sclerosis. 175 Jul 98

ION typically affects the older population with a sudden decrease in vision, altitudinal visual field loss, and a swollen optic nervehead. Systemic hypertension and diabetes mellitus are the most commonly associated medical problems. Occlusion of the posterior ciliary arterial blood supply to the retrolaminar optic nerve leads to axoplasmic stasis and further compromise of vessels in the nerve substance, which causes the typical funduscopic appearance. Although there is no recognized medical treatment that can reverse the visual loss, a recent report suggests optic nerve sheath decompression for a select group of patients with a gradual decline in vision due to ION may be beneficial. When ION occurs in persons less than 50 years of age, such etiologies as juvenile diabetes mellitus, antiphospholipid antibody-associated clotting disorders, collagen-vascular disease, and migraines should be considered. Rarely, complications of intraocular surgery or acute blood loss may cause an ischemic event in the optic nerve.
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PMID:Ischemic optic neuropathy. 201 Nov 5

Platelet function (as production of thromboxane B2 by platelets stimulated with collagen, and plasma beta-thromboglobulin) and thrombin activity (as plasma fibrinopeptide A) were investigated in eight young (mean age 27 +/- 3 SE years) male patients in which type 1 diabetes mellitus had been diagnosed 2 to 6 months previously. They were all in excellent stable metabolic control (mean HbA1c 5.6 +/- 0.4 SE %) and free from any complications. The haemostatic variables were assessed at rest and after cycloergometric exercise to exhaustion. When compared to age- and sex-matched healthy controls, patients showed higher beta-thromboglobulin, fibrinopeptide A and thromboxane B2 at rest. After exercise, plasma beta-TG increased only in the controls. Platelet and thrombin activation are present in the very early stages of type 1 diabetes mellitus, in the absence of any complications.
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PMID:Primary platelet activation in recent-onset type 1 diabetes mellitus. 214 55

We evaluated whether urinary excretion of the carboxy terminal domain (NC1) of Type IV collagen is associated with glomerular filtration rate and kidney size in Type I (insulin-dependent) diabetes mellitus (IDDM). Urinary excretion rate of NC1, glomerular filtration rate (GFR), and kidney size were measured in 16 men with Type I diabetes. Their mean age was 33.3 +/- 6.1 years with a duration of diabetes of 14.9 +/- 3.7 years (mean +/- SD). The urinary excretion rate of NC1 was higher in the diabetic patients than in 18 healthy control subjects. Urinary excretion of NC1 was associated with both kidney size, parenchymal width, and GFR (r = 0.73, p = 0.001; r = 0.63, p = 0.009; r = 0.53, p = 0.04, respectively). The exact relationship between these factors and basement membrane turnover/synthesis remains to be elucidated.
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PMID:Urinary excretion of the carboxy terminal domain of type IV collagen is associated with kidney size and function in IDDM. 215 Dec 28

Structure elucidation of a specific fluorophore from the aging extracellular matrix revealed the presence of a protein crosslink formed through nonenzymatic glycosylation of lysine and arginine residues. The unexpected finding that a pentose instead of a hexose is involved in the crosslinking process suggested that the crosslink, named pentosidine, might provide insight into abnormalities of pentose metabolism in aging and disease. This hypothesis was investigated by quantitating pentosidine in hydrolysates of 103 human skin specimens obtained randomly at autopsy. Pentosidine level was found to increase exponentially from 5 to 75 pmol/mg collagen over lifespan (r = 0.86, P less than 0.001). A three- to tenfold increase was noted in insulin-dependent diabetic and nondiabetic subjects with severe end-stage renal disease requiring hemodialysis (P less than 0.001). Moderately elevated levels were also noted in some very old subjects, some subjects with non-insulin dependent diabetes, and two subjects with cystic fibrosis and diabetes. The cause of the abnormal pentose metabolism in these conditions is unknown but may relate to hemolysis, impaired pentose excretion, cellular stress, and accelerated breakdown of ribonucleotides. Thus, pentosidine emerges as a useful tool for assessment of previously unrecognized disorders of pentose metabolism in aging and disease. Its presence in red blood cells and plasma proteins suggests that it might be used as a measure of integrated pentosemia in analogy to glycohemoglobin for the assessment of cumulative glycemia.
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PMID:End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. 229 12

Diabetic cheiroarthropathy (DCA) or pseudosclerodermatous hand of the diabetic is characterized by nonpainful limited extension of the proximal metacarpophalangeal and/or interphalangeal joints with spontaneous flexum of the fingers. The mechanism of lesion formation is poorly known but apparently associates neurogenic, vascular and cutaneous phenomena. Fifteen patients with DCA (9 men, 6 women; range 20-74 years) were studied by capillaroscopy, photoplethysmography and skin biopsy. Eleven had type 1 diabetes and 4 type 2 over periods ranging from 1 to 42 years (mean 19.9 years). Diabetic retinopathy was noted 10/15 times, nephropathy 5/15 times and neuropathy of the lower limbs 13/15 times. All patients had at least one of these abnormalities. In capillaroscopy, "Shoal of fish" features of diabetic microangiopathy were found only 4 times, but minor dystrophy was noted in 12 cases. In digital photoplethysmography, a drop in digital systolic pressure or an increase in pulse time was noted in 5 cases. The Hillestad test was less than or equal to 2 in 8 patients. Histological study showed constant dermal collagenous fibrosis in diseased skin, which was also found in normal skin in 6/13 patients. PAS staining showed a thickening of vascular basal membrane 14/15 times in diseased skin and 11/13 times in normal skin. The relation between DCA and microangiopathy is discussed in terms of collagen metabolism abnormalities observed during diabetes.
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PMID:[Diabetic cheiroarthropathy. Microcirculatory aspects]. 231 10

The early wound healing phases, and zinc and copper metabolism were assessed in traumatized insulin dependent diabetic rats. Granulation tissue was obtained by implanting Ivalon sponges subcutaneously and analysed on the fourth and seventh postoperative days by applying quantitative biochemical methods. The DNA content on day 4 and the amounts of RNA, hydroxyproline and hemoglobin on day 7 were significantly lower in granulation tissue from diabetic rats. The alkaline phosphatase activity, a marker for polymorphonuclear leukocytes (PMNs), was raised in the diabetic granulation tissue. The concentrations of zinc and copper were found to be increased in the kidney of diabetic rats compared with operated, non-diabetic controls. Our data suggest that the early granulation tissue formation is disturbed, with a prolonged inflammatory phase, decreased collagen formation and reduced vascularization. Zinc and copper are accumulated in the kidney of rats with uncontrolled, insulin dependent diabetes mellitus.
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PMID:Granulation tissue formation and metabolism of zinc and copper in alloxan-diabetic rats. 245 32


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